Treating Epileptic Seizures in Kids by the Clock

Tobias Loddenkemper,
a pediatric neurologist, works with some of the hardest epilepsy cases—the children whose seizures have been little helped by medication or surgery.

Nearly a third of epilepsy patients don't get sufficient relief from conventional drug treatments. But where advanced techniques don't help, Dr. Loddenkemper hopes a simple solution might: timing patients' medication to better coincide with their seizures.

Epilepsy, which affects 1% of the U.S. population, is a seizure disorder involving a surge of electricity in the brain. Its cause often isn't known, but in children the condition may be congenital or the result of a head injury. When medications can't control seizures, alternative treatments may be attempted, including surgery, strict diets and brain-stimulation techniques. But these have had limited success, according to the Epilepsy Foundation, a patient-advocacy group.

Dr. Loddenkemper, who works at Children's Hospital in Boston, is trying ways to make medication more effective by adjusting dosages based on when a person's seizures typically occur. This month the 39-year-old won the American Academy of Neurology's Dreifuss-Penry Epilepsy Award for young researchers for his work on treatment approaches.

Dr. Loddenkemper's approach seems basic. He asked his patients, or their parents, to keep seizure diaries, a standard practice. From those diaries, he noticed many patients had seizures around the same time every day, but often took the same dose of medication throughout the day. He changed their medication schedule so they took a higher dose when they most frequently had seizures.

"Why give the medication in the morning if the patient isn't having seizures then?" he says. "If they are having more seizures at night, give it to them at night." Although targeted dosing isn't new, "it's slowly growing" as a common treatment, he says. There has also been very little research on its effectiveness.

In a small study published last year in the journal Epilepsy & Behavior, Dr. Loddenkemper and several colleagues at Children's Hospital looked at 17 children who had seizures at night or in the early morning. The researchers varied the patients' doses to administer more of their anti-seizure medication when episodes were more likely to occur, while leaving the total dosage unchanged. After five months, 15 of the patients saw their seizures reduced by more than half, and 11 had become seizure-free.

Elaine Wirrell,
director of pediatric epilepsy at the Mayo Clinic in Rochester, Minn., who wasn't involved in the Children's Hospital research, said targeted dosing is sometimes tried if patients have a predilection for seizures at a specific time.

"It's not something that's usually in textbooks," she says. Having studies on the practice "legitimizes the practice and encourages it."

Dr. Loddenkemper became interested in epilepsy while in medical school in Germany, where he grew up. He focused on pediatric patients while at the Cleveland Clinic before moving to Boston in 2009. "It's heartbreaking when children lose developmental progress, they can struggle in school and seizures can lead to a social stigma," he says.

One of Dr. Loddenkemper's patients is Christopher Meredith-Walker, a 6-year-old in Brookline, Mass. Christopher started having seizures at age 2, says his mother, Tamara Meredith. He would go a few weeks or a month without having a seizure and then have several back-to-back in a week, she says.

Medications lessened the frequency of Christopher's seizures but didn't stop them, and they made him sleepy when he started school last year, Ms. Meredith says. Last summer, Dr. Loddenkemper changed the boy's routine so he took a higher level of two seizure medications—Trileptal and Keppra—at night and a smaller amount in the morning, she says.

"He hasn't had a seizure since August," says his mother. "Now he's able to participate and play. He's not sleeping in class anymore."

Part of the challenge in creating an individualized medication routine is determining when seizures typically occur, and patients' seizure journals aren't always accurate. Dr. Loddenkemper is working with
Rosalind Picard,
director of the Affective Computing Research Group at the Massachusetts Institute of Technology, to develop better ways of tracking seizures using wristband sensors that detect changes in the body's autonomic nervous system.

The sensors detect seizures about 94% of the time, says Dr. Picard. "Ideally, we'd like to use them to predict seizures, but we're not there yet," she says.

Dr. Loddenkemper also is studying other biomarkers that may be able to detect seizures, including levels of melatonin or cortisol. With children, "if you can make an impact early then they have a lifetime of freedom ahead of them," he says.

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